- Glioma Diagnosis and Treatment
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Brain Metastases and Treatment
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Apelin-related biomedical research
- RNA Interference and Gene Delivery
- Animal Virus Infections Studies
- Angiogenesis and VEGF in Cancer
- Nanoplatforms for cancer theranostics
- Mitochondrial Function and Pathology
- Immune cells in cancer
- MicroRNA in disease regulation
- Cancer Research and Treatments
- Lipid metabolism and disorders
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- Cancer Genomics and Diagnostics
- Medical Imaging Techniques and Applications
- Neurogenesis and neuroplasticity mechanisms
Haukeland University Hospital
2015-2024
University of Bergen
2015-2024
Qilu Hospital of Shandong University
2019-2023
Université de Bordeaux
2021
Luxembourg Institute of Health
2019
Institute for Biomedicine
2017
Universitätsmedizin Greifswald
2014
Institute for Community Health
2014
Laboratoire National de Santé
2012
Ålesund Hospital
2011
Bevacizumab, an antibody against vascular endothelial growth factor (VEGF), is a promising, yet controversial, drug in human glioblastoma treatment (GBM). Its effects on tumor burden, recurrence, and physiology are unclear. We therefore determined the response to bevacizumab at phenotypic, physiological, molecular level clinically relevant intracranial GBM xenograft model derived from patient spheroids. Using anatomical physiological magnetic resonance imaging (MRI), we show that causes...
The incidence of malignant melanoma is increasing worldwide in fair-skinned populations. Melanomas respond poorly to systemic therapy, and metastatic melanomas inevitably become fatal. Although spontaneous regression, likely due immune defense activation, rarely occurs, we lack a biological rationale predictive markers selecting patients for therapy.We performed unsupervised hierarchical clustering global gene expression data from stage IV 57 patients. For further characterization, used...
Abstract Increased somatic mitochondrial DNA (mtDNA) mutagenesis causes premature aging in mice, and mtDNA damage accumulates the human brain with neurodegenerative disorders such as Parkinson disease (PD). Here, we study complete spectrum of changes, including deletions, copy-number variation point mutations, single neurons from dopaminergic substantia nigra other areas individuals neurologically healthy controls. We show that individuals, copy number increases age, maintaining pool...
Abstract We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying role of THBS1 in glioblastoma (GBM) development. was found be increased with glioma grades. Mechanistically, we show that TGFβ canonical pathway transcriptionally regulates THBS1, through SMAD3 binding gene promoter. silencing inhibits tumour cell invasion and growth, alone combination anti-angiogenic therapy. Specific inhibition THBS1/CD47...
The transfer of intact mitochondria between heterogeneous cell types has been confirmed in various settings, including cancer. However, the functional implications on tumor biology are poorly understood. Here we show that is a prevalent phenomenon glioblastoma (GBM), most frequent and malignant primary brain tumor. We identified horizontal from astrocytes as mechanism enhances tumorigenesis GBM. This dependent network-forming intercellular connections GBM cells astrocytes, which facilitated...
Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited solid tumor tissue or even detects infiltrating parts.In 30 patients, a primary recurrent was suspected on imaging. Patients were investigated with [11C]MET-PET before biopsy. The trajectories plotted into...
Adult stem cells are promising cellular vehicles for therapy of malignant gliomas as they have the ability to migrate into these tumors and even track infiltrating tumor cells. However, their clinical use is limited by a low passaging capacity that impedes large-scale production. In present study, bone marrow–derived, highly proliferative subpopulation mesenchymal (MSCs)—here termed marrow–derived tumor-infiltrating (BM-TICs)—was genetically modified treatment glioma. Upon injection or...
Anti-angiogenic therapy in glioblastoma (GBM) has unfortunately not led to the anticipated improvement patient prognosis. We here describe how human GBM adapts bevacizumab treatment at metabolic level. By performing (13)C6-glucose flux analysis, we show for first time that tumors undergo re-programming toward anaerobic metabolism, thereby uncoupling glycolysis from oxidative phosphorylation. Following treatment, an increased influx of was observed into tumors, concomitant lactate levels and...
Angiogenesis is regarded as a hallmark of cancer progression and it has been postulated that solid tumor growth depends on angiogenesis. At present, however, clear cell invasion can occur without angiogenesis, phenomenon particularly evident by the infiltrative malignant brain tumors, such glioblastomas (GBMs). In these amplification or overexpression wild-type (wt) truncated constitutively activated epidermal factor receptor (EGFR) are important events in GBM development, where complex...
Abstract Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in tumour suppressor gene PTEN (phosphatase tensin homolog) are frequent events associated with therapeutic resistance. Herein, we report a novel chromatin-associated function complex histone chaperone DAXX variant H3.3. We show that interacts and, turn directly regulates oncogene expression by modulating DAXX-H3.3 association on chromatin, independently enzymatic activity. Furthermore,...
As cancer treatment tools, oncolytic viruses (OV) have yet to realize what some see as their ultimate clinical potential. In this study, we engineered a chimeric vesicular stomatitis virus (VSV) that is devoid of its natural neurotoxicity while retaining potent activity. The envelope glycoprotein (G) VSV was replaced with variant the lymphocytic choriomeningitis (LCMV-GP), creating replicating therapeutic, rVSV(GP), benign in normal brain but can effectively eliminate multiple preclinical...
Abstract Long non-coding RNAs play critical roles in tumour progression. Through analysis of publicly available genomic datasets, we found that MIR22HG, the host gene microRNAs miR-22-3p and miR-22-5p, is ranked among most dysregulated long glioblastoma. The main purpose this work was to determine impact MIR22HG on glioblastoma growth invasion elucidate its mechanistic function. MIR22HG/miR-22 axis highly expressed as well glioma stem-like cells compared normal neural stem cells. In...
Patient-based cancer models are essential tools for studying tumor biology and the assessment of drug responses in a translational context. We report establishment large cohort unique organoids patient-derived orthotopic xenografts (PDOX) various glioma subtypes, including gliomas with mutations IDH1, paired longitudinal PDOX from primary recurrent tumors same patient. show that PDOXs enable long-term propagation patient represent clinically relevant avatars retain histopathological,...
Mitochondrial complex I deficiency occurs in the substantia nigra of individuals with Parkinson's disease. It is generally believed that this phenomenon caused by accumulating mitochondrial DNA damage neurons and it contributes to process neurodegeneration. We hypothesized if these theories are correct, should extend beyond other affected brain regions disease correlate tightly neuronal damage. To test our hypothesis, we employed a combination semiquantitative immunohistochemical analyses,...
The role of mitochondria in the pathogenesis neurodegeneration is an area intense study. It known that defects proteins involved mitochondrial quality control can cause Parkinson's disease, and there increasing evidence linking dysfunction, particularly DNA abnormalities, to neuronal loss substantia nigra. Mutations catalytic subunit polymerase gamma are among most common causes disease owing its homeostasis, often considered a paradigm for diseases generally. Yet, despite this, parkinsonism...
Amplification of the epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are among most common genetic alterations in glioblastoma (GBM), frequent aggressive primary brain tumor.In present work, we analyzed clonal evolution these major EGFR aberrations a small cohort GBM patients using unique surgical multisampling technique. Furthermore, overexpressed both receptors separately together 2 patient-derived stem cell lines (GSCs) to analyze their functions vivo orthotopic xenograft...
Abstract Glioblastoma (GBM) is a deadly disease with need for deeper understanding and new therapeutic approaches. The microenvironment of glioblastoma has previously been shown to guide progression. In this study, astrocytes were investigated regard their effect on proliferation through correlative analyses clinical samples experimental in vitro vivo studies. Co‐culture techniques used investigate the GBM growth enhancing potential astrocytes. Cell sorting RNA sequencing generate...
Abstract Background Microtubes (MTs), cytoplasmic extensions of glioma cells, are important cell communication structures promoting invasion and treatment resistance through network formation. MTs abundant in chemoresistant gliomas, particular, glioblastomas (GBMs), while they uncommon chemosensitive IDH-mutant 1p/19q co-deleted oligodendrogliomas. The aim this study was to identify potential signaling pathways involved MT Methods Bioinformatics analysis TCGA performed analyze differences...